Oil-in-water emulsions have particular utility for the administration of drugs, cosmetics or other active agents to subjects, but are disadvantageous in that such emulsions have certain drawbacks with regard to their manufacture, transportation and storage. These include the bulk and weight of the water which is used to keep the oil in suspension, limited long term storage stability of the emulsion, the limited range of concentrations in which such emulsions are available and the risk of microbial growth in the aqueous phase, which can be an especially fertile breeding ground for microorganisms when amino acids or carbohydrates are included.
Lyophilization is a well known technique for processing and storage of moisture sensitive compounds. This methodology is employed in various applications in the food and pharmaceutical industries. For example, U.S. Pat. No. 4,616,047 relates to oral emulsions that are prepared by a method which includes the steps of preparing a lipid phase by stirring at a temperature of 80.degree. C. or less, preparing an aqueous phase by stirring an organic filler or thickening agent with water at a temperature of 80.degree. C. or less, introducing the lipid phase into the aqueous phase to form a homogeneous emulsion, distributing the emulsion into alveolar packs, freezing the contents of the packs at a temperature of between -20.degree. and -50.degree. C., and lyophilizing the frozen contents at between 80 and 0.13 Pa with a heat supply that is always lower than the melting temperature of the components. A pharmaceutically active substance can be incorporated into the emulsion prior to distribution into the alveolar packs.
Prior attempts to lyophilize oil-in-water emulsions, however, failed to preserve the original mean droplet size after reconstitution. Furthermore, enhanced bioavailability of the drug is achieved when the mean droplet size is in the submicron range.
In addition, successful lyophilization usually requires the use of large amounts of carbohydrates which may cause hypertonic solutions and high susceptibility for microbial contamination. For example, European Patent 211,257 relates to emulsion compositions that comprise carbohydrates which in some instances may be dangerous for diabetic patients and on some occasions are hyperosmotic after reconstitution. These emulsions are thus intended only for parenteral use and contain hydrophobic drugs.
It is also difficult to stabilize oil-in-water emulsions for the commercially desired two-year shelf-life. While this goal can sometimes be achieved if the emulsions are stored refrigerated, the use of refrigeration causes limitations on the distribution of the product. Moreover, the addition of drugs to emulsions generally results in increased instability and precludes a reasonable commercial product.
Therefore, it would be advantageous, both practically and economically, if emulsions could be produced as a dry product which can be reconstituted prior to use in order to facilitate the transport, storage and stability of such emulsions. It would also be desirable to provide an oil-in-water emulsion composition which is storage-stable, which can be sterilized easily, which is easily prepared in any desired concentration and which eliminates the opportunity for microbial growth if it becomes contaminated.